Single-cell RNA Sequencing Identified Novel Nr4a1⁺ Ear2⁺ Anti-Inflammatory Macrophage Phenotype under Myeloid-TLR4 Dependent Regulation in Anti-Glomerular Basement Membrane (GBM) Crescentic Glomerulonephritis (cGN).

ABSTRACT: Previously, this study demonstrates the critical role of myeloid specific TLR4 in macrophage-mediated progressive renal injury in anti-glomerular basement membrane (anti-GBM) crescentic glomerulonephritis (cGN); however, the underlying mechanism remains largely unknown. In this study, single-cell RNA sequencing (scRNA-seq), pseudotime trajectories reconstruction, and motif enrichment analysis are used, and macrophage diversity in anti-GBM cGN under tight regulation of myeloid-TLR4 is uncovered. Most significantly, a myeloid-TLR4 deletion-induced novel reparative macrophage phenotype (Nr4a1⁺ Ear2+) with significant upregulated anti-inflammatory and tissue repair-related signaling is discovered, thereby suppressing the M1 proinflammatory responses in anti-GBM cGN. This is further

SUBMITTER: Chen J 

PROVIDER: S-EPMC9218767 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature